Intramolecular Prins Reaction Research Articles

Total synthesis of a putative yuzurimine-type Daphniphyllum alkaloid C14‑epi-deoxycalyciphylline H

One of the largest subfamilies within the famous Daphniphyllum alkaloid family is made up of the yuzurimine-type (or macrodaphniphyllamine-type) alkaloids. Their complex aza-polycyclic caged structures, several contiguous stereogenic centers, and vicinal all-carbon quaternary centers make these alkaloids formidable challenge for synthetic chemists. Recently, synthesis of these alkaloids has received extensive attention from our community. Herein, we wish to report the total synthesis of C14‑epi-deoxycalyciphylline H, a putative member of yuzurimine-type alkaloid subfamily. Key transformations employed in our approach include an intramolecular Prins reaction and a Pd-catalyzed enyne cycloisomerization. In addition, synthesis of a daphnezomine L-type alkaloid, paxdaphnidine A, was also studied.

Bioinspired Total Synthesis of Erectones A and B, and the Revised Structure of Hyperelodione D

AbstractThe field of biomimetic synthesis seeks to apply biosynthetic hypotheses to the efficient construction of complex natural products. This approach can also guide the revision of incorrectly assigned structures. Herein, we describe the evolution of a concise total synthesis and structural reassignment of hyperelodione D, a tetracyclic meroterpenoid derived from a Hypericum plant, alongside some biogenetically related natural products, erectones A and B. The key step in the synthesis of hyperelodione D forms six stereocentres and three rings in a bioinspired cascade reaction that features an intermolecular Diels–Alder reaction, an intramolecular Prins reaction and a terminating cycloetherification.

Bioinspired Total Synthesis of Erectones A and B, and the Revised Structure of Hyperelodione D.

The field of biomimetic synthesis seeks to apply biosynthetic hypotheses to the efficient construction of complex natural products. This approach can also guide the revision of incorrectly assigned structures. Herein, we describe the evolution of a concise total synthesis and structural reassignment of hyperelodione D, a tetracyclic meroterpenoid derived from a Hypericum plant, alongside some biogenetically related natural products, erectones A and B. The key step in the synthesis of hyperelodione D forms six stereocentres and three rings in a bioinspired cascade reaction that features an intermolecular Diels–Alder reaction, an intramolecular Prins reaction and a terminating cycloetherification.

Cascade intramolecular Prins/Friedel-Crafts cyclization for the synthesis of 4-aryltetralin-2-ols and 5-aryltetrahydro-5H-benzo[7]annulen-7-ols.

The treatment of 2-(2-vinylphenyl)acetaldehydes or 3-(2-vinylphenyl)propanals with BF3·Et2O results in an intramolecular Prins reaction affording intermediary benzyl carbenium ions, which are then trapped by a variety of electron-rich aromatics via Friedel–Crafts alkylation. This cascade Prins/Friedel–Crafts cyclization protocol paves an expedient path to medicinally useful 4-aryltetralin-2-ol and 5-aryltetrahydro-5H-benzo[7]annulen-7-ol derivatives.

Tungsten oxide-based materials as effective catalysts in isopulegol formation by intramolecular Prins reaction of citronellal

Several types of mixed WO3/SiO2/Al2O3 materials were prepared using sol–gel and wet impregnation methods. Four different loadings of WO3 (1, 10, 25 and 40 wt%) were prepared. Materials were characterized using X-ray diffraction, X-ray fluorescence spectroscopy, and their acidity was measured by temperature programmed desorption of pyridine. Catalytic activity of these materials was tested in Prins reaction—intramolecular cyclization of citronellal. Influence of reaction conditions (temperature 70–90 °C, catalyst amount 1–10 wt%, catalyst type) on citronellal conversion and selectivity of isopulegol formation was monitored. The best result (90% of isopulegol, 97% selectivity of isopulegol formation, 24 h) was obtained using W25 IMP catalyst (10 wt%, 50 °C). Possibility of catalyst reuse was confirmed.

Synthesis of Oxa-Bridged Medium-Sized Carbocyclic Rings via Prins Cyclization.

Herein, we report a new method for the synthesis of oxa-bridged carbocyclic units based on intramolecular Prins reaction of dioxinones. Our new synthetic approach is flexible and practical and has been successfully applied to the preparation of highly functionalized seven-, eight-, and nine-membered carbocycles. The potential utility of this approach has also been demonstrated in a model study toward construction of the 7,8-fused ring system presented in neoabyssomicin D.

Correction: Highly selective aluminium-catalysed intramolecular Prins reaction for l-menthol synthesis

Correction for ‘Highly selective aluminium-catalysed intramolecular Prins reaction for l-menthol synthesis’ by H. Itoh et al., RSC Adv., 2014, 4, 61619–61623.

Highly selective aluminium-catalysed intramolecular Prins reaction for l-menthol synthesis

The perfect production of l-menthol.

Gold-Catalyzed Cyclization of Oxo-1,5-enynes

Cationic gold(I) complexes catalyze the cycloisomerization of oxo-1,5-enynes to form oxatricyclic derivatives through an intramolecular Prins reaction.

Intramolecular Prins Reactions of Vinylcyclopropanes with Aldehydes and Ketones: A New Synthesis of Semicyclic Conjugated Dienes.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

Total Synthesis and Olfactory Evaluation of (1R*,3S*,6S*,7S*,8S*)‐ 3‐Hydroxy‐6,8‐dimethyltricyclo[5.3.1.03,8]undecan‐2‐one: A New Synthetic Route to the Patchoulol Skeleton

AbstractThe superposition analysis of (–)‐patchoulol (1), the odorous principle of patchouli oil, with the recently discoveredhigh‐impact spirocyclic patchouli odorant (+)‐(1S,4R,5R,9S)‐1‐hydroxy‐1,4,7,7,9‐pentamethylspiro[4.5]decan‐2‐one (2) resulted in the question as to whether a patchoulolderivative in which the gem‐dimethyl group is replacedby a carbonyl function would be a powerful patchouliodorant. The total synthesis of the racemic superstructure (1R*,3S*,6S*,7S*,8S*)‐3‐hydroxy‐6,8‐dimethyltricyclo[5.3.1.03,8]undecan‐2‐one (3) was accomplished in 13 steps from the inexpensive commercial odorant Cyclal C (7) with a total yield of 7 %. Conversion of 7 to the corresponding enamine 8 and subsequent copper‐catalyzed oxidative degradation afforded 2,4‐dimethylcyclohex‐3‐enone (6), which was subjected to a Robinson annulation with 1,4‐dimethoxybutan‐2‐one (9). The carbonyl function of the resulting annulation product 10 was removed by LAH reduction, acylation with Ac2O, and dissolving metal reduction. The deoxygenated methyl enol ether 12 thus obtained was then cleaved by mild hydrolysis with oxalic acid, and the resulting 2,9‐dimethyl‐Δ1‐octalin‐5‐one (5) was hydroxymethylenated by Claisen ester condensation with ethyl formate to provide thecis‐configured (2Z)‐2,3,4,4a,8,8a‐hexahydro‐2‐(hydroxymethylene)‐4a,6‐dimethylnaphthalen‐1(7H)‐one (4). In a novel intramolecular Prins reaction with an equimolar amount of p‐toluenesulfonic acid monohydrate, the ideally preformed precursor 4 cyclized to (1R*,2R*,3S*,7R*,8S*)‐2‐hydroxy‐4,8‐dimethyltricyclo[5.3.1.03,8]undec‐4‐en‐11‐one (13), comprising the complete carbon framework of the target compound 3. A Barton–McCombie deoxygenation of the corresponding O‐phenoxythiocarbonyl derivative, followed by oxidation of the lithium enolate of the resulting ketone 14 with the molybdenum peroxide reagent MoO5–pyridine–DMPU, and the face‐selective hydrogenation of the obtained(1R*,3S*,7S*,8S*)‐3‐hydroxy‐6,8‐dimethyltricyclo[5.3.1.03,8]undec‐5‐en‐2‐one (15) concluded the synthesis of the target molecule 3, which was accompanied by its odorless C‐6 epimer epi‐3 in the ratio 84:16. Both the target structure 3 and its unsaturated precursor 15 possessed pronounced patchouli odors, albeit slightly weaker in threshold than (–)‐patchoulol (1). This proved the superposition analysis of the templates 1 and 2 to be correct and provided novel insight into the structural requirements of patchouli odorants. As 3 was an intermediate in a total synthesis of rac‐1, the synthesis also constitutes a new formal total synthesis of racemic patchoulol (rac‐1). (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)

Cover Picture: Total Synthesis and Olfactory Evaluation of (1R*,3S*,6S*,7S*,8S*)‐3‐Hydroxy‐6,8‐dimethyltricyclo[5.3.1.03,8]undecan‐2‐one: A New Synthetic Route to the Patchoulol Skeleton (Eur. J. Org. Chem. 6/2006)

AbstractThe cover picture shows the ketol soaring above the navel of an oriental belly dancer, which smells not “like teen spirit” but actually like patchouli. This is symbolized by the colors the sunlight is refracted into, the colors of the cashmere fabrics with which patchouli leaves first came to Europe. As bifunctional compounds of these molecular dimensions were known to be odorless, the pronounced patchouli odor is indeed very surprising. This ketol is a superstructure of (−)‐patchoulol and a recently discovered high‐impact spirocyclic patchouli odorant, and its odor proves this superposition analysis to be valid. Its total synthesis was accomplished in 13 steps with a total yield of 7% from the inexpensive commercial odorant Cyclal C, and features a novel intramolecular Prins reaction. This unusual access to the tricyclic homoisotwistane skeleton constitutes, in addition, a new formal total synthesis of patchoulol. All details are discussed in the article by P. Kraft et al. on p. 1403 ff.

Intramolecular Prins Reactions of Vinylcyclopropanes with Aldehydes and Ketones: A New Synthesis of Semicyclic Conjugated Dienes

Carbonyl compounds bearing pendant vinylcyclopropanes react with sulfonic acids to produce semicyclic conjugated dienes. These functionalized dienes can be readily elaborated into complex polycyclic compounds.

Synthesis of novel steroid-tetrahydroquinoline hybrid molecules and d-homosteroids by intramolecular cyclization reactions

Steroidal aryliminium salts were prepared from d- seco-pregnene aldehyde 2b, and their BF 3·OEt 2-catalyzed reactions were studied. The nature of the substituent R 1 in the anilines 3– 6 essentially influenced the chemoselectivity. Using unsubstituted 3, 4-methoxy- ( 4) or 4-bromoaniline ( 5), different tetrahydroquinoline derivatives 7a– 13a via intramolecular hetero Diels-Alder reaction were formed. In the case of 4-nitroaniline ( 6) the N-arylamino- d-homopregnane ( 14a) were also obtained. We assume, that an intramolecular Prins reaction led to this type of fluoro- d-homosteroid. The main products represent a new class of tetrahydroquinolino-androstenes.

Synthesis of Novel Halogen‐Containing D‐Homoestrone and 13α‐D‐Homoestrone Derivatives by Lewis Acid‐Induced Intramolecular Prins Reaction.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Synthesis of novel halogen-containing d-homoestrone and 13α- d-homoestrone derivatives by Lewis acid-induced intramolecular Prins reaction

A simple synthetic route has been developed for the synthesis of 16-halo- d-homosteroids in both the normal and 13-epiestrone series by the Lewis acid-catalyzed cyclization of an unsaturated secoestrone aldehyde and its 13α isomer.

Azepines from the intramolecular Prins cyclization of an aminoderivative of lapachol

Intramolecular Prins reaction of the 2-(2,2-dimethoxyethylamino)-3-(3-methyl-2-butenyl)-1,4-dihydro-1,4-naphthalene-6,11-dione, an amino derivative of lapachol, under hydrolytic conditions, yielded novel azepines condensed with the naphthoquinone nucleus of lapachol.

Lridals and Cycloiridals, Products of An Unusual Squalene Metabolism in Sword Lilies (lridaceae)

In search for the precursors of the irones, terpenoid C14-ketones, which are responsible for the violet like scent of the orris oil, a new family of hitherto unknown triterpenoids, the iridals, was found. The monocyclic parent compound iridal is derived from cyclization of epoxysqualene to a bicyclic intermediate and subsequent opening of ring A between C3 and C4, accompanied by a methyl and hydride shift. Up to today more than twenty different compounds of this family have been isolated, which are derived from iridal by desaturations, oxidations and cyclizations. The introduction of an additional double bond by a dehydrogenase into the terpenoid side chain leads to iridals with conjugated triene moiety. Addition of a methyl group from S-adenosylmethionine to the terminal double bond of the iridal side chain initiates the formation of a second cyclohexane ring. This way the cycloiridals are formed, which represent the precursors of the irones and dihydroirones. The odoriferous ketones are released after oxidative degradation of the bicyclic C31-triterpenoids. Even more remarkable is the formation of the spiroiridals, which can be seen as products of an intramolecular Prins reaction. The compounds are not only present as free triterpenols but also esterified with fatty acids. There is experimental evidence that the iridals serve the plants as membrane constituents and protect the tissue against oxidative damage and other noxious influences. The iridal esters may be used by the plant as a pool of these valuable compounds, which are released by enzymatic hydrolysis, whenever needed.

Novel Application of the Intramolecular Prins Reaction: (-)-Anisatin Model Study

Hydrolysis of the enol ethers 9a and 9b gave the aldehyde 10 which cyclized in situ to the alcohols 11a and 11b via an intramolecular Prins reaction. Further regio- and stereocontrolled elaboration of the alcohols 11a and 11b afforded the lactone diol 14.

14β-hxdroxy steroids - III. Synthesis of digoxigenin from deoxycholic acid

A new synthetic approach to cardenolides is discussed which employs singlet oxygen addition to dienol ethers and an intramolecular Prins reaction.